Lightweight wearable sensors (finger, toe, earlobe clip-on's) have been in wide use for monitoring hospital patients for the oxygen content in their blood, non-invasively, by detecting electromagnetic radiation in the near-infrared (“near IR”).
However, many chemical compounds in the blood or other bodily fluids, which are detectable analytes or detectable components of pathogens, are more clearly identified from their spectrum in the mid-infrared (“mid-IR”).
The source of these spectra typically arises from molecular vibrations due to the nature of the bonds within a molecule, and mediated by the molecular structure, so that each molecular species tend to have distinct spectra. The near IR spectra of many in vivo substances, such as glucose in blood, are obscured by spectral absorption peaks or plateaus in the spectrum of the water in blood, for example. However, these spectra tend to extend into the mid infrared (“mid IR”).
Typical spectrometers for the mid-IR tend to need cooling and are generally bulky and expensive, and are not suitable to be worn by a human or an animal, able to freely moving about and attending to regular business. There is a long-felt need for a wearable analyte detector which is accurate and remains in calibration.
In a molecule, the atoms are not held rigidly apart. Instead they can move, as if they are attached by a spring of equilibrium separation. See FIG. 1 (prior art). This bond can either bend or stretch. If the bond is subjected to infrared radiation of a specific frequency (between 300-4000 cm−1), it will absorb the energy, and the bond will move from the lowest vibration state, to the next highest. In a simple diatomic molecule, there is only one direction of vibrating, stretching. This means there is only one band of infrared absorption. Weaker bonds require less energy, as if the bonds are springs of different strengths. If there are more atoms, there will be more bonds, and therefore more modes of vibrations. This will produce a more complicated spectrum. For a linear molecule with “n” atoms, there are 3n−5 (for n=2 or greater) vibration modes, if it is nonlinear, it will have 3n−6 for (n>2) modes. These resonant frequencies are determined by the shape of the molecular potential energy surfaces, the masses of the atoms and, by the associated vibronic coupling. The resonant frequencies can be, in a first approximation to a description of the molecular system, related to the strength of the bond, and the mass of the atoms at either end of it. Thus, the frequency of the vibrations can be associated with a particular bond type. Measurement of physiological concentrations of compounds in vivo in situ in blood, such as glucose (“blood sugar”), or in saliva (or other bodily fluids) by infrared (IR) absorption spectroscopy is interfered with by water (and protein) absorption spectra. The spectral absorbance of water in the mid-IR does not obscure the 900-1500 cm−1 ‘fingerprint’ spectral bands and only partially obscures the 2700-3600 cm−1 spectral bands that are rich in characteristic absorbencies.
Thus, the rich mid-IR absorption texture of organic compounds and the diversity of the absorption bands for water result in potential compound quantifications, which are significantly better than for that of the near-IR.
Bodily fluids can be similarly analyzed in the mid-IR by applying the mid-IR spectral detector-analyzer to a transparent (in the mid IR) “cell,” or fluid holder, where the fluid may be a saliva sample or urine sample, for example, and which the spectral-detector clamps around, or, onto, rather than clamping around, or onto, a finger or an earlobe.
A reliable spectral analyzer, which has sufficient effective penetrative depth (by operating reliably in the mid-IR), to analyze in vivo blood glucose, or other fluid, “off-line”, in a cell, is believed to not exist heretofore.
Operating as a “pathometer,” a mid-IR spectral detector-analyzer, would answer a long-felt need, namely, as an apparatus, which would detect the antigenic materials or actual pathogens or pathogenic components from viruses, bacteria or pathogens from saliva, and fluid samples from ulcers or open sores after the collection of very small samples from these various sites.
Both type I and Type II diabetes are clinically controlled with insulin injections, typically taken at discrete times by pricking the skin so as to draw a droplet of blood and blotting on a paper test strip which then reads the “blood sugar” concentration and by the person with the diabetes regulating the blood sugar in vivo blood sugar concentration by discrete injections of insulin administered by hypodermic needle. There are also, known in the art, wearable insulin pumps which are typically programmed, or manually set, or by a combination of programming and manual setting set, to deliver insulation amounts on a more continuous basis into, in vivo, the bloodstream, via a pre-positioned hypodermic needle, or other means.
The “missing link” has heretofore been the glucose sensor. Although measurement of oxygenation by wearable or clip-on sensors is widely and routinely used for monitoring hospital patient, a similar application for blood sugar (glucose) has not so far blossomed. The reason is that the continuous measurement of glucose levels in the blood by a non-invasive technique requires a more subtle approach than the extrapolation of blood oxygen-level techniques by “brute force,” in the scientific sense.
Measuring physiological concentrations of glucose in blood by infrared (IR) absorption spectroscopy for glucose has concentrated on the near IR (4000-6000 cm−1), see FIG. 2 (prior art1) but interference from protein and water absorption spectra has precluded univariant calibration or glucose concentrations measurements. The 2%-5% absorbance for the glucose spectral bands (FIG. 2, prior art) exaggerates the spectral diversity of the near IR. The circled portion of the IR transmission curve between 4000-4600 cm−1 (FIG. 2, prior art2) puts this in perspective. In FIG. 4 (prior art), the misrepresentation is magnified by referencing relative absorbance {0-1} rather than actual absorbance (0.02-0.05). FIG. 4 (prior art) also demonstrates that these glucose absorbencies, weak though they be, are masked by protein and water absorption.
Glucose exhibits a high spectral diversity, since there are more than twenty absorption peaks over the mid IR. As shown in FIG. 3 (prior art) these absorption peaks are between 2700-3600 cm−1 and 900-1500 cm−1. The spectral absorbance of water in the mid IR (FIG. 5, prior art) does not obscure the 900-1500 cm−1 spectrum and the spectral absorption of Bovine Albumin (plasma matrix) in the IR (FIG. 6, prior art) only partially obscures the 2700-3600 cm−1 and 900-1500 cm−1 spectrums that are two of the spectral bands rich in glucose absorbance (FIG. 7, prior art).
The rich mid-IR absorption texture of glucose and the diversity of the absorption bands for water and plasma matrix result in a potential glucose quantification, which will be significantly better than for that of the near-IR. The spectral diversity will also improve the discrimination potential of component regression techniques and provide more spectra for component regression analysis spectroscopy.